A Phase 2 Study of Sorafenib (BAY 43-9006) in Metastatic Renal Cell Cancer to the Brain

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed renal cell carcinoma metastatic to the
brain

- Measurable disease in the brain

- Meets 1 of the following criteria:

- No prior brain-specific therapy AND no CNS symptoms referable to the brain
lesion(s) (with or without concurrent steroid therapy)

- CNS symptoms referable to the brain lesion(s) AND received primary therapy for
the brain lesion(s)

PATIENT CHARACTERISTICS:

- Blood pressure < 140/90 mm Hg on 2 separate occasions, taken at least 24 hours apart,
within the past 6 weeks (patients on stable anti-hypertensive regimens allowed)

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Bilirubin < 1.5 times upper limit of normal (ULN)

- ALT/AST < 2.5 times ULN

- Estimated glomerular filtration rate > 30 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to swallow pills or comply with an oral treatment regimen

- No history of a bleeding diathesis or requirement for full-dose anticoagulation

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to sorafenib

- No clinical or radiologic evidence of bowel obstruction or perforation

- No other uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would limit compliance with study
requirements

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
and recovered

- More than 4 weeks since prior radiotherapy to sites outside of the brain and
recovered

- More than 8 weeks since prior standard external-beam radiotherapy to the brain unless
there is evidence of in-brain progression

- No prior complete surgical resection or radiosurgery of all known brain metastases
unless there is evidence of in-brain progression

- No prior sorafenib, sunitinib malate, bevacizumab, or any other agent targeting the
platelet-derived growth factor receptor (PDGFR) or vascular endothelial growth factor
receptor (VEGFR) kinase cascade

- No other concurrent investigational agents

- No concurrent enzyme-inducing anti-seizure medications, including phenytoin,
phenobarbital, carbamazepine, or primidone

- Concurrent non-enzyme-inducing anti-seizure medications allowed

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent hematopoietic growth factors except erythropoietin

- No concurrent ketoconazole, itraconazole, or ritonavir

- No concurrent grapefruit juice

- No concurrent Hypericum perforatum (St. John's wort)

- No concurrent chemotherapy

- No concurrent hormonal therapy except steroids for adrenal failure and/or control of
CNS edema or hormones for non-disease related conditions (e.g., insulin for diabetes)

- No concurrent palliative radiotherapy

- No other concurrent anticancer therapy

- Concurrent bisphosphonates allowed